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Drug resistance in the cancer cells is a leading cause of mortality during the cancer treatment. ABC transporters expressed in the cancer cells have been found to extrude anticancer drugs from the inside of the cells to their outside for the protection of the cells from the drugs, resulting in the drug resistance. However, the mechanisms of how cancer cells acquire ABC transporter-mediated drug resistance have not yet been fully understood. Therefore, numerous strategies have been tested or proposed to control the functions and the expressions of ABC transporter genes so far. The first strategy utilized to inhibit ABC transporter function relied on the identification of nonchemotherapeutic agents as competitors. Other approaches have included the use of hammerhead ribozymes against the ABC transporter genes and the gene-targeted antisense oligonucleotides. On the other hand, recently, epigenetic modifications of the genes have been emerging as a part cause of ABC transporter-mediated drug resistance. In this chapter, therefore, epigenetic modifications of the ABC transporter genes are covered, where the outlines of the regulatory mechanisms and factors involved in the epigenetic modifications are described, focusing on the best known mechanisms in human such as DNA methylation/demethylation and posttranslational modifications of histone proteins. Furthermore, drugs affecting epigenetic modifications are also introduced and described from a viewpoint of ABC transporter-mediated drug resistance in this chapter. We hope that this chapter can provide new insights into the understanding of cancer cells to acquire drug resistance, which could lead us to conquering the ABC transporter-mediated drug resistance. |
